Dlg gene is found to be expressed ubiquitously in many tissues and cells. Dlg gene encodes a protein (hereinafter, may be referred to Dlg) which is reported to bind to APC (adenomatous polyposis coli) via the C-terminal XVT motif of APC (Non-Patent Reference 1). APC gene was isolated as a responsible gene for familial adenomatous polyposis (hereinafter, may be referred to FAP). An abnormal APC gene has been detected in FAP and also in many cases of sporadic colorectal tumor. This suggests that the abnormal APC gene may be an important factor for onset of colorectal cancer. In addition, over-expression of APC blocks cell cycle progression. The expression of both Dlg and APC was found in rat colon epithelial cells and at the synapse in cultured hippocampal neurons. These findings suggest that the Dlg-APC complex may participate in regulation of both cell cycle progression and neuronal function.
APC gene encodes a large protein of 300 kDa (hereinafter, may be referred to APC) which forms a complex with β-catenin and negatively regulates Wnt/Wingless signal (hereinafter, may be referred to Wnt signal) transduction pathway. The Wnt signal was found as a signal transduction system involved in regulation of morphogenesis, and is known to participate in numerous events including development, regulation of stem cell differentiation, and tumor formation. Recently, the Wnt signal was reported to be an important factor for stem cell in its proliferation regulation and survival (Non-Patent References 2 and 3).
The Wnt signal induced by Wnt ligand is transduced into a cell via a frizzled membrane receptor (hereinafter, may be referred to Fz) on the cell membrane.
In recent years, a secretory protein that binds to both Fz and Wnt, namely sFRP, was found out (Non-Patent Reference 4). sFRP binds to Fz and Wnt outside a cell and works as an antagonist of the Wnt signal, and thereby participates in regulation of the Wnt signal (Non-Patent Reference 5). In addition, it was reported that the sFRP function was reduced in a colorectal cancer cell due to methylation of sFRP gene and that restoration of the sFRP function in a colorectal cancer cell induced reduction of the Wnt signal in the cell (Non-Patent Reference 6).
Non-patent Reference 1: Matsumine, A. et al., Science, 1996, Vol. 272, p. 1020-1023.
Non-patent Reference 2: Willert, K. et al., Nature, 2003, Vol. 423, p. 448-452.
Non-patent Reference 3: Reya, T. et al., Nature, 2003, Vol. 423, p. 409-414.
Non-patent Reference 4: Kawano, Y. et al., Journal of Cell Science, 2003, Vol. 116, p. 2627-2634.
Non-patent Reference 5: Jones, S. E. et al., BioEssays, 2002, Vol. 24, p. 811-820.
Non-patent Reference 6: Suzuki, H. et al., Nature Genetics, 2004, Vol. 36, p. 417-422 (published online on Mar. 14, 2004).